P
US11529392B2ActiveUtilityPatentIndex 63

Carrier-free biologically-active protein nanostructures

Assignee: MASSACHUSETTS INST TECHNOLOGYPriority: Sep 27, 2013Filed: Feb 19, 2020Granted: Dec 20, 2022
Est. expirySep 27, 2033(~7.2 yrs left)· nominal 20-yr term from priority
Inventors:TANG LIIRVINE DARRELL J
Y10T428/2982A61K 47/54A61K 47/6813A61P 3/10C07K 2319/30A61K 47/6835A61K 47/60A61K 38/2086A61K 38/2013A61P 9/00A61K 47/6903A61P 37/06A61P 35/00
63
PatentIndex Score
0
Cited by
362
References
40
Claims

Abstract

The present disclosure provides compositions and methods for efficient and effective protein delivery in vitro and in vivo. In some aspects, proteins are reversibly crosslinked to each other and/or modified with functional groups and protected from protease degradation by a polymer-based or silica-based nanoshell.

Claims

exact text as granted — not AI-modified
What is claimed is: 
     
       1. A nanostructure comprising a plurality of immunostimulatory proteins reversibly crosslinked to each other through a degradable linker that degrades under physiological conditions to release the immunostimulatory proteins, wherein the immunostimulatory proteins are immunostimulatory cytokines, antigens, or immunostimulatory antibodies or antibody fragments. 
     
     
       2. The nanostructure of  claim 1 , wherein the immunostimulatory proteins are immunostimulatory cytokines. 
     
     
       3. The nanostructure of  claim 2 , wherein the immunostimulatory cytokines are IL-2, IL-7, IL-15, IL-15 superagonist, IFN-gamma, IFN-alpha, GM-CSF, or FLT3-ligand. 
     
     
       4. The nanostructure of  claim 2 , wherein the immunostimulatory cytokines are IL-15 or IL-15 superagonist. 
     
     
       5. The nanostructure of  claim 1 , wherein the immunostimulatory proteins are fusion proteins. 
     
     
       6. The nanostructure of  claim 1 , further comprising a polymer. 
     
     
       7. The nanostructure of  claim 6 , wherein the polymer is surface conjugated to the nanostructure. 
     
     
       8. The nanostructure of  claim 7 , wherein the polymer is covalently conjugated. 
     
     
       9. The nanostructure of  claim 7 , wherein the polymer is non- covalently conjugated. 
     
     
       10. The nanostructure of  claim 6 , wherein the polymer comprises poly(ethylene oxide), polylactic acid, poly(lactic-co-glycolic acid), polyethylene glycol, polyglutamate, or polylysine. 
     
     
       11. The nanostructure of  claim 1 , wherein the nanostructure is conjugated to the surface of a carrier cell. 
     
     
       12. The nanostructure of  claim 11 , wherein the carrier cell is an engineered carrier cell. 
     
     
       13. The nanostructure of  claim 11 , wherein the carrier cell is lymphocyte. 
     
     
       14. The nanostructure of  claim 13 , wherein the lymphocyte is an NK cell, a B cells, a T cell, a CD4+T cell, a CD8+T cell, a cytotoxic T cell, or a NK T cell. 
     
     
       15. The nanostructure of  claim 14 , wherein the lymphocyte is genetically engineered. 
     
     
       16. The nanostructure of  claim 13 , wherein the lymphocyte is specific to a tumor antigen. 
     
     
       17. The nanostructure of  claim 11 , wherein the nanostructure is noncovalently conjugated to the surface of the carrier cell. 
     
     
       18. A composition comprising a plurality of nanostructures, each nanostructure comprising a plurality of immunostimulatory proteins reversibly crosslinked to each other through a degradable linker that degrades under physiological conditions to release the immunostimulatory proteins, wherein the immunostimulatory proteins are immunostimulatory cytokines, antigens, or immunostimulatory antibodies or antibody fragments. 
     
     
       19. The composition of  claim 18 , wherein the immunostimulatory proteins are immunostimulatory cytokine. 
     
     
       20. The composition of  claim 19 , wherein the immunostimulatory cytokines are IL-2, IL-7, IL-15, IL-15 superagonist, IL-12, IFN-gamma, IFN-alpha, GM-CSF, or FLT3-ligand. 
     
     
       21. The composition of  claim 19 , wherein the immunostimulatory cytokines are IL-15 or IL-15 superagonist. 
     
     
       22. The composition of  claim 18 , wherein the immunostimulatory proteins are fusion proteins. 
     
     
       23. The composition of  claim 18 , further comprising a polymer. 
     
     
       24. The composition of  claim 23 , wherein the polymer is surface conjugated to the nanostructure. 
     
     
       25. The composition of  claim 24 , wherein the polymer is covalently conjugated. 
     
     
       26. The composition of  claim 24 , wherein the polymer is non- covalently conjugated. 
     
     
       27. The composition of  claim 23 , wherein the polymer comprises poly(ethylene oxide), polylactic acid, poly(lactic-co-glycolic acid), polyethylene glycol, polyglutamate, or polylysine. 
     
     
       28. The composition of  claim 18 , wherein the plurality of nanostructures are conjugated to the surface of a carrier cell. 
     
     
       29. The composition of  claim 28 , wherein the carrier cell is an engineered carrier cell. 
     
     
       30. The composition of  claim 28 , wherein the carrier cell is a lymphocyte. 
     
     
       31. The composition of  claim 30 , wherein the lymphocyte is an NK cell, a B cells, a T cell, a CD4+T cell, a CD8+T cell, a cytotoxic T cell, or a NK T cell. 
     
     
       32. The composition of  claim 31 , wherein the lymphocyte is genetically engineered. 
     
     
       33. The composition of  claim 30 , wherein the lymphocyte is specific to a tumor antigen. 
     
     
       34. The composition of  claim 30 , wherein the plurality of nanostructures are noncovalently conjugated to the surface of the carrier cell. 
     
     
       35. A method of treating a condition or a disease in a subject, comprising administering the nanostructure of  claim 1 . 
     
     
       36. The method of  claim 35 , wherein the condition or disease is cancer, diabetes, an autoimmune disease, or a cardiovascular disease. 
     
     
       37. The method of  claim 35 , wherein the nanostructure is administered by oral, intravenous, intraperitoneal, intramuscular, intracavity, intratumor, or transdermal route of administration. 
     
     
       38. A method of treating a condition or a disease in a subject, comprising administering the nanostructure of  claim 18 . 
     
     
       39. The method of  claim 38 , wherein the condition or disease is cancer, diabetes, an autoimmune disease, or a cardiovascular disease. 
     
     
       40. The method of  claim 38 , wherein the nanostructure is administered by oral, intravenous, intraperitoneal, intramuscular, intracavity, intratumor, or transdermal route of administration.

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